Innovative Computational Tool Unveils Concealed DNA Changes in Cancer Linked to Treatment Resistance

Significant genetic alterations in cancer often remain hidden, posing challenges in diagnosis and treatment. These structural changes within a tumor's DNA may drive aggressive growth and frequently go undetected by conventional testing methods, particularly when tissue samples are limited or compromised.

Researchers at the Mayo Clinic have introduced a groundbreaking computational tool named BACDAC, designed to reveal these elusive genomic alterations. This innovative tool enables the identification of genomic instability through comprehensive DNA sequencing, even in samples with low purity or coverage.

BACDAC aims to enhance clinicians' ability to predict tumor behavior and tailor treatment strategies accordingly. Central to its functionality is the concept of ploidy, which refers to the number of complete sets of chromosomes within a cell. While healthy human cells typically possess two sets (totaling 46 chromosomes), cancer cells often exhibit significant gains or losses, disrupting this balance and facilitating uncontrolled growth.

In a recent study published in Genome Biology, the research team utilized BACDAC to analyze over 650 tumors spanning 12 different cancer types. The findings revealed instances of whole-genome doubling, a phenomenon where a tumor replicates its entire DNA, a condition often associated with aggressive cancer characteristics and resistance to treatment.

According to George Vasmatzis, a lead researcher on the project, the implementation of BACDAC provides unprecedented insight into genomic layers previously hidden from view. The development of this tool marks a significant milestone in the ongoing effort to translate decades of research on genomic instability into practical applications.

BACDAC also features a visual representation of a tumor's genomic landscape through a unique output called the Constellation Plot, which offers an intuitive overview of chromosome stability. This visual aid is expected to assist researchers and pathologists in interpreting results more effectively.

Moving forward, the Mayo Clinic team plans to further validate BACDAC with the goal of evolving it into a clinically applicable diagnostic tool. This advancement could play a crucial role in informing treatment decisions by providing clearer insights into structural changes within tumors.